DESCRIPTION: Papillomaviruses are important human pathogens whose biology is still incompletely understood. This grant is focused on unraveling the repertoire of proteins required for papillomavirus DNA replication in vitro. Reconstituting viral DNA synthesis in vitro has been used before as an invaluable means of understanding the host's replication machinery. Such experiments with SV40 have provided tremendous insight into the basic DNA replication apparatus within mammalian cells. The repertoire of purified proteins sufficient to direct SV40 DNA snthesis in vitro is not sufficient to direct papillomavirus DNA synthesis in vitro. The major goal of this grant is to isolate and characterize the remaining celllular activities required for papillomavirus DNA replication.